Final, Long-Term Safety Results for Diazepam Nasal Spray in Patients Aged 2-5 Years From a Phase 1/2a Study
Abstract number :
3.357
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2025
Submission ID :
887
Source :
www.aesnet.org
Presentation date :
12/8/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Eric Segal, MD – Hackensack University Medical Center and Northeast Regional Epilepsy Group and Hackensack Meridian School of Medicine
James Wheless, BScPharm, MD, FAAP, FACP, FAAN, FAES, FCNS – University of Tennessee Health Science Center and Le Bonheur Children's Hospital
Jurriaan Peters, MD PhD – Boston Children's Hospital
Steven M Wolf, MD – Westchester Medical Center, Hawthorne, NY, United States
Muhammad Zafar, MD – Duke University School of Medicine
Charles Davis, PhD – CSD Biostatistics, Inc.
Miguel Lopez-Toledano, PhD – Neurelis, Inc.
Leock Ngo, PhD – Neurelis, Inc.
Adrian Rabinowicz, MD – Neurelis, Inc., Center for Molecular Biology and Biotechnology (CMBB) in the Charles E. Schmidt Collage of Science at Florida Atlantic University
Enrique Carrazana, MD – Neurelis, Inc., John A. Burns School of Medicine; University of Hawaii, Honolulu, HI
Rationale: The US Food and Drug Administration (FDA) expanded the approved age range for diazepam nasal spray for the acute treatment of seizure clusters in patients with epilepsy, which now includes pediatric patients aged 2 to 5 y (April 2025). Diazepam nasal spray does not require positioning the patient, needs fewer steps to administer than diazepam rectal gel, and has an established safety profile in patients aged 6-17 y that is consistent with rectal diazepam in children ≥6 y and adults. Long-term safety of diazepam nasal spray in patients 2-5 y with epilepsy was evaluated from a phase 1/2a, open-label pharmacokinetics (PK) study of diazepam nasal spray that included a 180-day open-label safety period and an optional extension period (until the patient reached age 6 or study termination; NCT05076838).
Methods: Patients aged 2-5 y with partial or generalized epilepsy with motor seizures or seizures with clear alteration of awareness were enrolled. Doses were based on the patient’s body weight (0.5 mg/kg). Following a single dose for PK assessment, caregivers were supplied with diazepam nasal spray to use on an as-needed basis for immediate treatment of seizure clusters during the safety and optional extension periods. Patients returned to the site on days 30, 90, and 180, and then every 90 days thereafter, for safety evaluations, including recording of treatment-emergent adverse events (TEAEs).
Results: The study enrolled 36 patients and was conducted between November 8, 2021, and April 28, 2025. Thirty-one patients (86.1%) completed the 180-day safety period, and 27 enrolled in and completed the optional extension period. Mean age was 3.9 y (range: 2.0-5.8 y); 19 (52.8%) and 17 (47.2%) of the enrolled patients were 2-3 y and 4-5 y, respectively. Mean duration of exposure to diazepam nasal spray was 15.45 months (SD, 8.4).TEAEs, treatment-related TEAEs, and serious TEAEs were reported in 24 (66.7%), 7 (19.4%), and 10 (27.8%) patients, respectively, during the open-label safety period, and in 24 (88.9%), 1 (3.7%), and 7 (25.9%) patients, respectively, during the optional extension period (Table). Serious TEAEs related to depressed respiration were reported for 1 patient in the open-label safety period (respiratory depression) and 2 in the optional extension period (acute respiratory failure, respiratory failure); none were investigator-assessed as treatment related. No other serious TEAEs were considered treatment related, and no TEAEs led to discontinuation or death. No sudden unexpected death in epilepsy (SUDEP) was reported during the study. Status epilepticus was reported in 1 patient (2.8%) during the open-label safety period and in 4 (14.8%) patients during the optional extension period. All status epilepticus events were not treatment related, and all resolved.
Conclusions: The safety profile of diazepam nasal spray was generally consistent with that of older patients and confirms the safety profile of diazepam nasal spray and age- and weight-based dosing in this younger age group of patients aged 2-5 y.
Funding: Neurelis, Inc.
Anti-seizure Medications